We have developed a new assay for daily monitoring of intragraft events after renal transplantation in man. Fine needle aspiration biopsies of approximately 10-20 Mu1 in volume are drawn from renal transplants without risk to the transplant or the transplant recipient. From transplant aspiration cytology we can (a) evaluate the condition of the graft parenchymal component; (b) quantitate the expression of the major locus (and other) antigens on the graft parenchymal (and inflammatory) cells, and (c) quantitate the onset, size, type and duration of the in situ inflammatory response of rejection. We will utilize this technology in prerandomized clinical trials to evaluate the in situ mode(s) of action of different immunosuppressive and anti-inflammatory drugs in renal allograft rejection. The immunosuppressive effects will be evaluated in prophylactic trials: Prerandomized patient groups will receive for immunosuppression (i) azathioprine (AZA) plus low dose methyl-prednisolone (MP), (ii) AZA plus high dose MP, (iii) cyclosporin A (CyA), (iv) CyA plus MP, or (v) AZA, low dose MP and (monoclonal) anti-T cell serum (ATS). The impact of the treatment on the graft, on the display of graft MHC antigens and on the onset, size and type of the (first) in situ inflammatory episode(s) of rejection are monitored by transplant aspiration cytology. The anti-inflammatory effects are examined in therapeutic trials: Patients treated with a single immunosuppressive regime (probably AZA plus high initial MP) are randomized at the onset of the first in situ episode of inflammation (i.e., rejection) for the following treatment groups: (i) oral low dose MP, (ii) intravenous high dose MP, (iii) (monoclonal) ATS, (iv) CyA, (v) local irradiation or (vi) nothing at all. The impact of the treatment on the size, type and duration of the in situ inflammatory response of rejection will be quantitated. We believe that our approach will help to define the site(s) of action of these drugs on the intragraft immune and inflammatory effects, provide a basis for logical and more discriminate use of these drugs, lead to steroid-sparing or steroid-free immunosuppressive programs and hopefully to less complications and better impact on patient therapy.